Development of efficient enzyme replacement therapy for lysosomal storage disease with immune modulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Ohashi Toya 東京慈恵会医科大学, 医学部, 教授 (60160595)
• Co-Investigator(Kenkyū-buntansha): 嶋田 洋太 東京慈恵会医科大学, 医学部, 助教 (20560824) ; 樋口 孝 東京慈恵会医科大学, 医学部, 助教 (30595327) ; 小林 博司 東京慈恵会医科大学, 医学部, 准教授 (90266619) ; 横井 健太郎 東京慈恵会医科大学, 医学部, 講師 (20459655)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 遺伝・先天異常 / 先天代謝異常症 / 酵素補充療法 / 免疫寛容 / ライソゾーム病 / 抗体

Outline of Final Research Achievements

Lysosomal storage disease (LSD) are characterized by genetic deficiency of lysosomal enzyme, resulting in accumulation of its substrate in various organ.
As a treatment, enzyme replacement therapy (ERT) is available. ERT is very efficient, but immune reaction against infused enzyme was occurred. This causes development of neutralizing antibody. ERT has another limitation, which is ineffectiveness to brain disease because of presence of BBB. To overcome these two problem, we tested various approach. The positive results were obtained following two experiment. (1)Anti-Blys antibody successfully reduce immune reaction of ERT on murine model of Fabry disease and increased efficacy of ERT. (2)Huge amount of enzyme administration reduced accumulated compound in brain from mucopolysaccharidosis type II mice without immune reaction against enzyme by anti-CD3 antibody administration.

Free Research Field

先天代謝異常症